DZNep inhibits H3K27me3 deposition and delays retinal degeneration in the rd1 mice

Cell Death & Disease
Shijie ZhengDanian Chen

Abstract

Retinitis pigmentosa (RP) is a group of inherited retinal degenerative diseases causing progressive loss of photoreceptors. Numerous gene mutations are identified to be related with RP, but epigenetic modifications may also be involved in the pathogenesis. Previous studies suggested that both DNA methylation and histone acetylation regulate photoreceptor cell death in RP mouse models. However, the role of histone methylation in RP has never been investigated. In this study, we found that trimethylation of several lysine sites of histone H3, including lysine 27 (H3K27me3), increased in the retinas of rd1 mice. Histone methylation inhibitor DZNep significantly reduced the calpain activity, delayed the photoreceptor loss, and improved ERG response of rd1 retina. RNA-sequencing indicated that DZNep synergistically acts on several molecular pathways that regulate photoreceptor survival in rd1 retina, including PI3K-Akt and photoreceptor differentiation pathways, revealing the therapeutic potential of DZNep for RP treatment. PI3K-Akt pathway and H3K27me3 form a feedback loop in rd1 retina, thus PI3K inhibitor LY294002 reduces phosphorylation of Ezh2 at serine 21 and enhances H3K27me3 deposition, and inhibiting H3K27me3 by DZNep can a...Continue Reading

References

Nov 6, 2001·Nature Genetics·A J MearsA Swaroop
Aug 2, 2002·Trends in Biochemical Sciences·Robert SchneiderTony Kouzarides
May 6, 2003·Journal of Cell Science·Monika LachnerThomas Jenuwein
Jan 20, 2004·Molecular and Cellular Biology·Krishna Murthi VasudevanVivek M Rangnekar
Jun 24, 2004·Seminars in Cell & Developmental Biology·Alfonso MoraDario R Alessi
Jan 22, 2005·Trends in Genetics : TIG·Avril KennanPete Humphries
Mar 23, 2005·Current Opinion in Cell Biology·Antoine H F M Peters, Dirk Schübeler
Dec 17, 2005·Nature·Emmanuelle ViréFrançois Fuks
Jan 13, 2006·Journal of Neurochemistry·Francois Paquet-DurandPer Ekström
Mar 28, 2006·Investigative Ophthalmology & Visual Science·Catherine JomaryStephen E Jones
Nov 8, 2006·Proceedings of the National Academy of Sciences of the United States of America·Daniela SangesValeria Marigo
Nov 23, 2006·Lancet·Dyonne T HartongThaddeus P Dryja
Nov 5, 2008·Molecular Neurobiology·Javier Sancho-PelluzFrançois Paquet-Durand
Jan 10, 2009·Science·Bo Chen, Constance L Cepko
Mar 25, 2009·Nature Reviews. Genetics·Howard Cedar, Yehudit Bergman
Jun 11, 2009·Molecular Cancer Therapeutics·Tina Branscombe MirandaPeter A Jones
Apr 10, 2010·Nature Reviews. Molecular Cell Biology·Bart VanhaesebroeckBenoit Bilanges
Aug 18, 2010·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Keisuke NimuraYasufumi Kaneda
Dec 16, 2010·Nature Reviews. Molecular Cell Biology·Roberto ZoncuDavid M Sabatini
Jan 21, 2011·Nature·Raphaël Margueron, Danny Reinberg
Mar 3, 2011·Cell Death & Disease·J Sancho-PelluzP Ekström
Dec 2, 2011·Current Genomics·Stefano FerrariFrancesco Parmeggiani
Jan 2, 2013·Frontiers in Bioscience (Scholar Edition)·Janusz BlasiakKai Kaarniranta
Jan 30, 2013·Proceedings of the National Academy of Sciences of the United States of America·Dusan ZencakYvan Arsenijevic
Sep 1, 2011·Journal of Ocular Biology, Diseases, and Informatics·Rajesh C RaoShiming Chen
Apr 17, 2013·BMC Bioinformatics·Edward Y ChenAvi Ma'ayan
Mar 4, 2014·Journal of Cell Science·Steve Jean, Amy A Kiger
Nov 14, 2014·PloS One·Blanca Arango-GonzalezFrançois Paquet-Durand
Dec 6, 2014·Cell Death & Disease·P FarinelliP A R Ekström
Dec 8, 2014·Diabetologia·Marpadga A ReddyRama Natarajan
Jan 6, 2015·Developmental Neurobiology·Atsumi IidaSumiko Watanabe
Jan 24, 2015·Investigative Ophthalmology & Visual Science·Shijie ZhengBo Lei

❮ Previous
Next ❯

Citations

Dec 5, 2019·BMJ Open Ophthalmology·Katie KerrAmy Jayne McKnight
Jun 21, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shan-Shan WanYan-Ning Yang
Apr 2, 2019·Frontiers in Neuroscience·Eric Murillo-RodríguezAndré Barciela Veras
Jan 4, 2019·Human Genetics·Cheryl Y Gregory-EvansKevin Gregory-Evans
Nov 2, 2019·Investigative Ophthalmology & Visual Science·Salma FerdousJohn M Nickerson
Dec 17, 2020·Frontiers in Neuroscience·Jelena PoticYvan Arsenijevic
Aug 3, 2019·Progress in Retinal and Eye Research·Michael PowerFrançois Paquet-Durand
Feb 11, 2021·Epigenetics & Chromatin·Reza RaeisossadatiJeffrey M Gross
Jul 13, 2021·Experimental Eye Research·Zhongping LvDanian Chen

❮ Previous
Next ❯

Methods Mentioned

BETA
immunoprecipitation
acetylation
Assay
dissecting
PCR

Software Mentioned

Adobe Illustrator
custom
MaxQuant
Image J
Andromeda
EpiQuik
GraphPad Prism
Tophat2
FastQC
R script

Related Concepts

Related Feeds

Ataxia telangiectasia (MDS)

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.